Many materials, particularly fluids, are passed through porous media to separate or remove certain materials. In particular, biological fluids, containing a variety of components and constituents, are typically passed through porous media for such purposes. For example, it is sometimes desirable to separate whole blood into one or more component parts and/or to remove a cellular constituent such as leucocytes from whole blood or a blood component. Thus, improved porous media and separation techniques are desirable to separate and/or remove a component or constituent from a fluid.
The depletion of deleterious matter in biological fluids administered to a patient for therapeutic reasons is of considerable importance to avoid potential harmful effects on the recipient of the fluid. Of particular importance is the depletion of deleterious matter, especially leucocytes, from biological fluids such as blood and blood products used in transfusions and in extracorporeal circuits to prevent or reduce reperfusion injury, as well as a number of other diseases and conditions.
It has been the practice for many years to transfuse whole blood, and more recently blood components, from one or more donors to other persons. With the passage of time and the accumulation of research and clinical data, transfusion practices have improved greatly. One aspect of current practice is that whole blood is rarely administered; rather, patients needing red blood cells are given packed red cells (hereinafter PRC), and patients needing platelets are given platelet concentrate (hereinafter PC). These components are typically separated from whole blood by centrifuging, the process providing, as a third product, plasma, from which various other useful components are obtained.
In addition to the three above-listed components, whole blood contains white blood cells (known collectively as leucocytes) of various types, of which the most important are granulocytes and lymphocytes. In the donor, white blood cells provide protection against bacterial and viral infection.
However, the transfusion of any leucocyte-containing fluid, such as packed red cells or whole blood containing donor leucocytes may be harmful to the recipient. Some of the viral diseases induced by transfusion therapy, e.g., Cytomegaloviral Inclusion Disease, which is a life threatening infection to newborns and debilitated adults, are transmitted by the infusion of homologous leucocytes. Another life-threatening phenomenon affecting immunocompromised patients is Graft versus host disease (GVH), a disease in which the transfused leucocytes actually cause irreversible damage to the blood recipient's organs as well as the skin, gastrointestinal tract and neurological system. In this clinical syndrome, donor lymphocytes transfused with the platelet preparations can launch an immunological reaction against the host, i.e. the transfusion recipient, with pathological consequences. Conventional red cell transfusions have also been indicted as adversely influencing the survival of patients undergoing surgery for malignancy of the large intestine. It is believed that this adverse effect is mediated by the transfusion of agents other than donor red blood cells, including the donor's leucocytes.
The transfusion of platelet concentrate is also not without risk for those patients receiving both acute and chronic transfusion support. Chills, fever and allergic reactions may occur in patients receiving acute as well as chronic platelet therapy. Repeated platelet transfusions frequently leads to alloimmunization against HLA antigens, as well as platelet specific antigens. This in turn decreases responsiveness to platelet transfusion. Leucocytes contaminating platelet concentrates, including granulocytes and lymphocytes, are associated with both febrile reactions and alloimmunization leading to platelet transfusion refractoriness. Another potential consequence of platelet transfusion is the transmission of bacterial, viral, and parasitic infectious diseases.
In the currently used centrifugal methods for separating blood into the three basic fractions (packed red cells, platelet concentrate, and plasma), the leucocytes are present in substantial quantities in both the packed red cells and platelet concentrate fractions. It is generally accepted that it would be highly desirable to reduce the leucocyte concentration of these blood components to as low a level as possible. While there is no firm criterion, it is generally accepted that many of the undesirable effects of transfusion would be reduced if the leucocyte content were reduced by a factor of about 100 or more prior to administration to the patient. This approximates reducing the total content of leucocytes in a single unit of PRC (the quantity of PRC obtained from a single blood donation) to less than about 1.times.10.sup.7. Recently it has become more widely perceived that in order to prevent viral infection by transfused blood, factors of reduction should be more than 100, preferably more than 1000, and more preferably 30,000 or 100,000 fold or more, such as 1,000,000 fold.
One of the most effective means of reducing leucocyte content is disclosed in U.S. Pat. No. 4,925,572, which is directed towards the bedside filtration of PRC.
Accordingly, it is a primary object of the present invention to provide a separatory or removal porous medium through which a fluid, particularly a biological fluid, may be passed. It is another object of the invention to provide a porous medium capable of depleting deleterious matter from biological fluids. It is a further object of the invention to provide a porous medium that is capable of depleting leucocytes from blood and blood products. It is a more specific object of this invention to provide a porous medium that has been treated with a gas plasma to improve the ability of the medium to deplete deleterious matter, especially leucocytes (and more specifically granulocytic neutrophils), from biological fluids such as blood and blood products. Another object of the invention is to provide a porous medium which allows the passage of a significant amount of platelets therethrough. These and other objects and advantages of the present invention will become apparent to those skilled in the art in view of the following detailed description.